408 INFECTION AND RESISTANCE 



Madsen 76 and by Kretz. 77 The last-named worker observed that horses 

 that had been immunized with diphtheria toxin would often react to 

 neutral mixtures of toxin and antitoxin by which normal horses were 

 unaffected. This so-called "paradox phenomenon" was much dis- 

 cussed, and many theories advanced to explain it, a most ingenious 

 adaptation of the side-chain theory being applied to it by Kretz 78 

 and by Wassermann. 79 They assumed that the partial immunization 

 in such treated animals had in truth induced the formation of ex- 

 cessive receptors ; that, in the stages of hypersusceptibility, however, 

 these receptors had not yet been cast off from the cells. In conse- 

 quence there was an excess of "sessile receptors" by means of 

 which the cell was rendered more exposed to toxin action than it was 

 normally it being still unprotected by the presence of freely cir- 

 culating "antitoxin" receptors. The difficulties arising from the 

 observation of similar hypersusceptibility in animals whose blood 

 contained free antitoxin were disposed of by Wassermann by the 

 convenient assumption of variations of affinity. 



He assumed that the treatment with toxin, i. e., the intoxication, 

 may induce a condition of higher affinity for the poison on the part 

 of the sessile cell receptors, leading to a selective toxin-absorption by 

 the cells and consequent greater susceptibility to injury. With 

 Behring, he speaks of this as a "histogenic hypersusceptibility," 

 implying an increased vulnerability of the tissue cells. 



The analogy between these early observations and the phenomena 

 which we now classify as anaphylaxis is unquestionably a striking 

 one. However, it is doubtful, as Friedemann suggests, whether the 

 two processes depend upon similar mechanisms. For, as we have 

 seen in the case of the sensitiveness to toxin, we are dealing with 

 primarily poisonous substances against which in the reacting animal 

 neutralizing antibodies are found a combination of conditions quite 

 different from those with which we are confronted in hypersuscepti- 

 bility against primarily harmless proteins. It is, of course, possible 

 that the toxin hypersusceptibility is a true anaphylaxis against the 

 toxin-protein independent of the specifically poisonous nature of 

 this substance. However, this is unlikely, since Lowi and Meyer 8( 

 have shown that with tetanus toxin, the symptoms of such hypersus- 

 ceptibility are not those of anaphylaxis, but of increased but charac- 

 teristic tetanus poisoning. The fact that toxin hypersusceptibility 

 cannot be passively transferred with the serum of a susceptible ani- 

 mal does not seem to us a good argument against its anaphylactic na- 



76 Salomonsen et Madsen. Ann. de I'Inst. Past., 1897. 

 "Kretz. Quoted from Otto in "Kolle u. Wassermann Handbuch," Er- 

 ganzungsband 2, p. 232. 



78 Kretz. Zeitschr. f. Heilkunde, 1902. 



79 Wassermann. "Kolle u. Wassermann Handbuch," Vol. 4, p. 479. 



80 Lowi and Meyer. Festschrift. Schmiedeberg Suppl., Arch. f. exp. Path. 

 u. Therap, 1908, p. 355. 



